BASIC RESEARCH FOR CEREBRAL WHITE MATTER DEMENTIA USING MODELS OF RADIATION-INDUCED DEMENTIA RATS
Project/Area Number |
07457307
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
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Research Institution | NIIGATA UNIVERSITY |
Principal Investigator |
TAKEUCHI Shigekazu NIIGATA UNIV.BRAIN RES.INST.ASSISTANT PROFESSOR, 脳研究所, 助教授 (50143772)
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Co-Investigator(Kenkyū-buntansha) |
ABE Hiroshi NIIGATA UNIV.MEDICAL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (60240769)
MORI Ken NIIGATA UNIV.BRAIN RES.INST.ASSISTANT, 脳研究所, 助手 (20230089)
MORI Hiroshi NIIGATA UNIV.BRAIN RES.INST.ASSISTANT, 脳研究所, 助手 (70291359)
藤井 幸彦 新潟大学, 医学部付属病院, 助手 (40283014)
佐藤 光弥 新潟大学, 医学部・附属病院, 助手 (10235400)
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Project Period (FY) |
1996 – 1997
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Project Status |
Completed (Fiscal Year 1997)
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Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥3,200,000 (Direct Cost: ¥3,200,000)
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Keywords | radiation / rat / water maze / passive avordance / apoptosis / GFAP |
Research Abstract |
A course of whole brain irradiation (30Gy (group A) or 25Gy (group B) /single dose, 40Gy/5Gy*8/4weeks (groupC)) was administered to Fischer 344 rats aged just 6 month, while control rats received sham irradiation (group D) to develop a model of radiation-induced learning disability and to examine histologically. A passive avoidance and a Morris water maze task were studied in groups A and C at 6,9 and 12 months postirradiation, and were studied in group B at 12 months postirradiation. Then those rats were examined histologically and immunohistochemically using grial fibrirally acidic protein (GFAP). No learning disabilities nor radiaion necrosis were shown in groups A and C at 6 months after irradiadtion. But GFAP positive astrocytes were slightly increaced in the white matter in group A.At 9 months after irradiadtion, learning disabilities were shown obviously in group A and a little in group C.Many of group A showed radiation necrosis in the fimbria, internal capsule and corpus callo
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sum, while no radiation necrosis were shown in group C.And moderate increase in GFAP positive astrocytes in the white matter were shown in group A.At 12 months after irradiadtion, learning disabilities were shown in groups of A,B and C.The degree of the learning disability were A>B>C.All of group A showed single or multiple radiation necrosis in the fimbria, internal capsule and corpus callosum. And 60% of group B showed radiation necrosis only in the corpus callosum. While no radiation necrosis were shown in group C.And GFAP positive astrocytes were increaced in the white matter (A>B>C) in groups of A,B and C.These phenomena were like so-called that of white matter dementia such as multiple sclerosis or Binswanger syndrome which were recently often reported. In conclusion learning disability can be demonstrated following radiation therapy in rats. We have then irradiated right hemisphere of Fischer 344 neonatal rats and examined subsequent change of apoptosis in the white matter. Fischer 344 rats at the age of 7 days were employed. The right hemisphere was irradiated at a single dose of 5,10 and 15Gy. Apoptosis was examined with in situ apoptosis detection kit (Apop Tag ; Oncor corporation) at 2,3,6hours, 1,3, and 5 days post-irradiation. In the irradiated hemisphere apoptotic cells were found in the subcortical white matter, hippocampal dentate gyrus (HDG) and subependymal layr of the lateral ventricule at 3th after irradiation. Apoptotic cells were increaced in the HDG and periventricular white matter, and appeared in the internal capsule at 6th after irradiation. The numbers of those positive cells were peaked at 12h after in 15Gy irradiation group and 24h after in 5 and 10Gy irradiation group. And no apoptotic cells were observed in any regions at 5d after irradiation. The results suggest that apoptosis is closely related to injury of cerebral white matter caused by the irradiation insult at the acute phase. Less
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Report
(4 results)
Research Products
(2 results)